Tirasemtiv May Slow Respiratory Decline in ALS

Results of a large-scale trial of tirasemtiv in ALS show the drug may slow respiratory decline without improving scores on the ALS Functional Rating Scale

Tirasemtiv may have had positive effects on respiratory function in patients with ALS.

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Cytokinetics, developer of tirasmetiv, an experimental drug developed to treat amyotrophic lateral sclerosis, announced April 29, 2014, that the drug may have positive effects on respiratory function, qualifying a report the previous week that tirasemtiv failed to improve scores on the ALS Functional Rating Scale.

Gastrointestinal side effects such as nausea and loss of appetite were more common in the tirasemtiv than in the placebo group, and weight loss was greater in the tirasemtiv-treated participants as well; Cytokinetics says these factors may be responsible for the lack of benefit on the ALS Functional Rating Scale.

Cyotkinetics says it will continue to analyze the results of the tirasemtiv trial, known as BENEFIT-ALS, to understand how to approach further development of this drug.

The experimental drug tirasemtiv, in development by South San Francisco biopharmaceutical company Cyokinetics as a potential treatment for amyotrophic lateral sclerosis (ALS), slowed the decline in at least one measure of respiratory function in a recent, large-scale study known as BENEFIT-ALS (Blinded Evaluation of Neuromuscular Effects and Functional Improvement with Tirasemtiv in ALS).

The April 29 announcement qualifies the disappointing results reported five days earlier, noting, "Treatment with tirasemtiv resulted in a statistically significant and potentially clinically meaningful reduction in the decline of slow vital capacity (SVC, a measure of the strength of the skeletal muscles responsible for breathing) that has been shown to be an important predictor of disease progression and survival in prior trials of patients with ALS."

Gastrointestinal problems and weight loss may have contributed to the disappointing results on the ALS Functional Rating Scale, the company said, noting that trial participants on tirasemtiv experienced more nausea and loss of appetite and lost more weight than those taking the placebo.

"Adverse events on tirasemtiv in BENEFIT-ALS may have confounded certain results of the trial," said Andrew Wolff, chief medical officer and senior vice president of clinical research and development at Cytokinetics. "We will continue to analyze the results of BENIEFT-ALS to understand how to approach the potential further development of tirasemtiv."